烯丙基酚而非荧光素能增强成骨细胞中 PGD2 刺激的骨保护素和白细胞介素-6 的合成

IF 3
{"title":"烯丙基酚而非荧光素能增强成骨细胞中 PGD2 刺激的骨保护素和白细胞介素-6 的合成","authors":"","doi":"10.1016/j.plefa.2024.102639","DOIUrl":null,"url":null,"abstract":"<div><p>Gallein, a small molecule related to fluorescein, is established as an inhibitor of Gβγ subunits to inhibit G protein (Gs) signaling. This agent is providing a potential therapeutic strategy to ameliorate organ dysfunctions especially involved in inflammation, however; the effects on bone metabolism have not yet been clarified. Prostaglandins (PGs) play important roles as autacoids including osteoblasts, and <span>d</span>-type prostanoid (DP) receptor, a member of G protein-coupled receptor specific to PGD<sub>2</sub>, is expressed on osteoblasts. We previously reported that prostaglandin D<sub>2</sub> (PGD<sub>2</sub>) induces the syntheses of osteoprotegerin (OPG) and interleukin-6 (IL-6), essential factors in bone remodelling process, and p38 mitogen-activated protein kinase (MAPK), c-<em>Jun</em> N-terminal kinase (JNK), and p44/p42 MAPK are involved in the signal transduction of PGD<sub>2</sub> in osteoblast-like MC3T3-E1 cells. Thus, we investigated in this study that the effect and the underlying mechanism of gallein, an inhibitor Gβɤ subunits, on the syntheses of OPG and IL-6 induced by PGD<sub>2</sub> in these cells. The cultured cells were treated with gallein or fluorescein, a structurally related compound inactive to Gβɤ subunits, and subsequently stimulated with PGD<sub>2</sub>. Not fluorescein but gallein amplified the PGD<sub>2</sub>-stimulated releases of OPG and IL-6. Gallein enhanced the PGD<sub>2</sub>-upregulated mRNA expression levels of OPG and IL-6. Regarding the signaling mechanism, gallein did not affect the PGD<sub>2</sub>-induced phosphorylation of p38 MAPK, JNK, or p42 MAPK. In conclusion, gallein upregulates the PGD<sub>2</sub>-stimulated syntheses of OPG and IL-6 by the specific effect to inhibit Gβγ subunits in osteoblasts, but the effect is not exerted at the upstream of p38 MAPK, JNK, or p44/p42 MAPK activation.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Gallein but not fluorescein enhances the PGD2-stimulated synthesis of osteoprotegerin and interleukin-6 in osteoblasts\",\"authors\":\"\",\"doi\":\"10.1016/j.plefa.2024.102639\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Gallein, a small molecule related to fluorescein, is established as an inhibitor of Gβγ subunits to inhibit G protein (Gs) signaling. This agent is providing a potential therapeutic strategy to ameliorate organ dysfunctions especially involved in inflammation, however; the effects on bone metabolism have not yet been clarified. Prostaglandins (PGs) play important roles as autacoids including osteoblasts, and <span>d</span>-type prostanoid (DP) receptor, a member of G protein-coupled receptor specific to PGD<sub>2</sub>, is expressed on osteoblasts. We previously reported that prostaglandin D<sub>2</sub> (PGD<sub>2</sub>) induces the syntheses of osteoprotegerin (OPG) and interleukin-6 (IL-6), essential factors in bone remodelling process, and p38 mitogen-activated protein kinase (MAPK), c-<em>Jun</em> N-terminal kinase (JNK), and p44/p42 MAPK are involved in the signal transduction of PGD<sub>2</sub> in osteoblast-like MC3T3-E1 cells. Thus, we investigated in this study that the effect and the underlying mechanism of gallein, an inhibitor Gβɤ subunits, on the syntheses of OPG and IL-6 induced by PGD<sub>2</sub> in these cells. The cultured cells were treated with gallein or fluorescein, a structurally related compound inactive to Gβɤ subunits, and subsequently stimulated with PGD<sub>2</sub>. Not fluorescein but gallein amplified the PGD<sub>2</sub>-stimulated releases of OPG and IL-6. Gallein enhanced the PGD<sub>2</sub>-upregulated mRNA expression levels of OPG and IL-6. Regarding the signaling mechanism, gallein did not affect the PGD<sub>2</sub>-induced phosphorylation of p38 MAPK, JNK, or p42 MAPK. In conclusion, gallein upregulates the PGD<sub>2</sub>-stimulated syntheses of OPG and IL-6 by the specific effect to inhibit Gβγ subunits in osteoblasts, but the effect is not exerted at the upstream of p38 MAPK, JNK, or p44/p42 MAPK activation.</p></div>\",\"PeriodicalId\":94179,\"journal\":{\"name\":\"Prostaglandins, leukotrienes, and essential fatty acids\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2024-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Prostaglandins, leukotrienes, and essential fatty acids\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0952327824000334\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Prostaglandins, leukotrienes, and essential fatty acids","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0952327824000334","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

Gallein 是一种与荧光素有关的小分子,被认为是 Gβγ 亚基的抑制剂,可抑制 G 蛋白(Gs)信号传导。这种药剂是一种潜在的治疗策略,可改善器官功能障碍,尤其是与炎症有关的器官功能障碍,但其对骨代谢的影响尚未明确。前列腺素(PGs)在成骨细胞中发挥着重要的自分泌作用,d 型前列腺素(DP)受体是 G 蛋白偶联受体的成员之一,对 PGD2 具有特异性,可在成骨细胞中表达。我们以前曾报道过,前列腺素 D2(PGD2)可诱导骨重塑过程中必不可少的骨保护素(OPG)和白细胞介素-6(IL-6)的合成,而 p38 丝裂原活化蛋白激酶(MAPK)、c-Jun N 端激酶(JNK)和 p44/p42 MAPK 参与了 PGD2 在成骨细胞样 MC3T3-E1 细胞中的信号转导。因此,我们在本研究中探讨了 Gβɤ 亚基抑制剂 gallein 对 PGD2 诱导的 OPG 和 IL-6 合成的影响及其内在机制。用加勒林或荧光素(一种对 Gβɤ 亚基无活性的结构相关化合物)处理培养细胞,然后用 PGD2 刺激细胞。不是荧光素而是加来林扩大了 PGD2 刺激的 OPG 和 IL-6 的释放。加来宁增强了 PGD2 上调的 OPG 和 IL-6 的 mRNA 表达水平。在信号传导机制方面,加来林没有影响 PGD2 诱导的 p38 MAPK、JNK 或 p42 MAPK 的磷酸化。总之,加来林通过抑制成骨细胞中Gβγ亚基的特异性作用来上调PGD2刺激的OPG和IL-6的合成,但这种作用并不是在p38 MAPK、JNK或p44/p42 MAPK激活的上游发挥的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Gallein but not fluorescein enhances the PGD2-stimulated synthesis of osteoprotegerin and interleukin-6 in osteoblasts

Gallein, a small molecule related to fluorescein, is established as an inhibitor of Gβγ subunits to inhibit G protein (Gs) signaling. This agent is providing a potential therapeutic strategy to ameliorate organ dysfunctions especially involved in inflammation, however; the effects on bone metabolism have not yet been clarified. Prostaglandins (PGs) play important roles as autacoids including osteoblasts, and d-type prostanoid (DP) receptor, a member of G protein-coupled receptor specific to PGD2, is expressed on osteoblasts. We previously reported that prostaglandin D2 (PGD2) induces the syntheses of osteoprotegerin (OPG) and interleukin-6 (IL-6), essential factors in bone remodelling process, and p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and p44/p42 MAPK are involved in the signal transduction of PGD2 in osteoblast-like MC3T3-E1 cells. Thus, we investigated in this study that the effect and the underlying mechanism of gallein, an inhibitor Gβɤ subunits, on the syntheses of OPG and IL-6 induced by PGD2 in these cells. The cultured cells were treated with gallein or fluorescein, a structurally related compound inactive to Gβɤ subunits, and subsequently stimulated with PGD2. Not fluorescein but gallein amplified the PGD2-stimulated releases of OPG and IL-6. Gallein enhanced the PGD2-upregulated mRNA expression levels of OPG and IL-6. Regarding the signaling mechanism, gallein did not affect the PGD2-induced phosphorylation of p38 MAPK, JNK, or p42 MAPK. In conclusion, gallein upregulates the PGD2-stimulated syntheses of OPG and IL-6 by the specific effect to inhibit Gβγ subunits in osteoblasts, but the effect is not exerted at the upstream of p38 MAPK, JNK, or p44/p42 MAPK activation.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Prostaglandins, leukotrienes, and essential fatty acids
Prostaglandins, leukotrienes, and essential fatty acids Clinical Biochemistry, Endocrinology, Diabetes and Metabolism
CiteScore
5.30
自引率
0.00%
发文量
0
审稿时长
64 days
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信